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RNA 甲基转移酶 NSUN2 通过增强 mC 依赖性 TEAD1 表达促进下咽鳞状细胞癌的增殖和迁移。

RNA methyltransferase NSUN2 promotes hypopharyngeal squamous cell carcinoma proliferation and migration by enhancing TEAD1 expression in an mC-dependent manner.

机构信息

Department of Otolaryngology: Head and Neck Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.

Department of Otolaryngology: Head and Neck Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, China.

出版信息

Exp Cell Res. 2021 Jul 15;404(2):112664. doi: 10.1016/j.yexcr.2021.112664. Epub 2021 May 26.

Abstract

RNA methyltransferase NSUN2 is involved in cell proliferation and invasion in a variety of tumors. However, the expression, function, and mechanism of NSUN2 in hypopharyngeal squamous cell carcinoma (HPSCC) remains unknown. We used a bioinformatics database, polymerase chain reaction, cell culture and transfection, immunohistochemistry, cell proliferation assay, wound healing experiments, transwell assays, western blotting, RNA-seq detection, dual-luciferase reporter assay, in vivo experiments, and a dot blot assay to evaluate the role of NSUN2 in HPSCC. NSUN2 mRNA and protein were highly expressed in HPSCC; NSUN2 knockdown in vitro and in vivo decreased cell proliferation and invasion. Studies have shown that TEAD1, a transcription factor, may act downstream of NSUN2 in HPSCC. NSUN2 was found to promote the proliferation and invasion of HPSCC by upregulating TEAD1 in an 5-methylcytosine-dependent manner, thereby representing an oncogene and potential new target for treating HPSCC.

摘要

RNA 甲基转移酶 NSUN2 参与多种肿瘤的细胞增殖和侵袭。然而,NSUN2 在下咽鳞状细胞癌(HPSCC)中的表达、功能和机制尚不清楚。我们使用生物信息学数据库、聚合酶链反应、细胞培养和转染、免疫组织化学、细胞增殖测定、划痕愈合实验、Transwell 测定、Western blot、RNA-seq 检测、双荧光素酶报告基因检测、体内实验和点印迹实验来评估 NSUN2 在 HPSCC 中的作用。NSUN2 mRNA 和蛋白在上皮性下咽癌中高表达;体外和体内敲低 NSUN2 可降低细胞增殖和侵袭。研究表明,转录因子 TEAD1 可能在下咽鳞状细胞癌中作为 NSUN2 的下游因子发挥作用。研究发现,NSUN2 通过以 5-甲基胞嘧啶依赖的方式上调 TEAD1,促进 HPSCC 的增殖和侵袭,从而代表了一种癌基因和治疗 HPSCC 的潜在新靶点。

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